What is the typical chemotherapy regimen for neuroblastoma?

Neuroblastoma Chemotherapy Regimens

The preferred chemotherapy regimens for high-risk neuroblastoma are the 5-cycle ANBL12P1 or ANBL1531 induction protocols, which include combinations of topotecan, cyclophosphamide, cisplatin, etoposide, and doxorubicin, followed by consolidation with tandem transplantation using high-dose chemotherapy. 1

Induction Therapy for High-Risk Neuroblastoma

Induction therapy aims to reduce disease burden before subsequent treatment phases through:

• Multiagent cytoreductive chemotherapy combined with surgical resection of primary tumor and locoregional disease 1
• Collection of autologous peripheral blood stem cells during induction to support later consolidation therapy 1

Preferred Induction Regimens:

• ANBL12P1 or ANBL1531 (5-cycle regimens) - These are the NCCN-preferred protocols with:

  • Cycles 1-2: Topotecan and cyclophosphamide 1
  • Subsequent cycles: Cisplatin-based and alkylator-intensive combinations 1
  • Response rate: Approximately 80% of patients achieve partial response or better 1

• ANBL0532 (6-cycle regimen) - An acceptable alternative regimen 1

  • Similar components but with longer duration
  • Demonstrated 39.1% partial response or better after first 2 cycles with topotecan and cyclophosphamide 1

Evolution of Induction Regimens:

The development of these protocols has been driven by:

• Need to reduce exposure to nephrotoxic and cardiotoxic agents while maintaining efficacy 1
• Evidence that 5-cycle induction achieves comparable response rates to longer 7-cycle regimens 1
• Approximately 9% of patients progress despite intensive regimens 1

Surgical Considerations During Induction:

• Upfront resection is rarely feasible due to aggressive nature of tumors 1
• Surgical resection typically performed after several cycles of cytoreductive chemotherapy 1
• Goal is gross total resection (>90% resection) rather than negative margins 1
• Subtotal resection is recommended when vital structures would be threatened 1

Consolidation Therapy

For patients who respond adequately to induction therapy:

• Tandem transplantation with two consecutive rounds of high-dose chemotherapy with autologous stem cell rescue is recommended (Category 1) 1

  • First transplant: Thiotepa/cyclophosphamide
  • Second transplant: Reduced-dose carboplatin/etoposide/melphalan (CEM)
  • This approach showed significantly improved 3-year EFS (61.6% vs 48.4%) compared to single transplant 1

• Busulfan and melphalan (BuMel) is preferred in European protocols based on superior EFS compared to CEM 1, 2

  • However, higher risk of sinusoidal obstruction syndrome with BuMel 1

Special Considerations

• For certain subgroups with more favorable high-risk disease, single transplant may be appropriate 1:

  • Stage L2, ≥18 months, unfavorable histology, MYCN non-amplified
  • Stage M, 12 to <18 months, MYCN non-amplified with unfavorable histology, diploid DNA, or SCAs

• Patients with progressive disease during induction are not candidates for consolidation therapy and should receive non-myeloablative therapies 1

• Patients with minor response or stable disease after induction require individualized approaches 1

Historical Regimens and Research

Earlier studies established the efficacy of several agents now incorporated into modern protocols:

• Cyclophosphamide has demonstrated significant activity in neuroblastoma 3, 4
• Platinum agents (cisplatin and carboplatin) have shown effectiveness even in refractory disease 5
• Dose-intensive regimens with shorter intervals between treatments may improve outcomes 6

Common Pitfalls and Caveats

• No single regimen has been proven superior in prospective randomized trials comparing North American induction regimens 1
• Investigational approaches such as early addition of ALK inhibitors or anti-GD2 antibody therapy should only be used in clinical trials 1
• Toxicity management is crucial, particularly myelosuppression, mucositis, and hearing deficits 4
• Response assessment at the end of induction is critical for determining subsequent therapy 1